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. 1994 Mar 1;91(5):1824–1828. doi: 10.1073/pnas.91.5.1824

Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance.

A B Dollins 1, I V Zhdanova 1, R J Wurtman 1, H J Lynch 1, M H Deng 1
PMCID: PMC43256  PMID: 8127888

Abstract

We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin doses tested significantly increased sleep duration, as well as self-reported sleepiness and fatigue, relative to placebo. Moreover, all of the doses significantly decreased sleep-onset latency, oral temperature, and the number of correct responses on the Wilkinson auditory vigilance task. These data indicate that orally administered melatonin can be a highly potent hypnotic agent; they also suggest that the physiological increase in serum melatonin levels, which occurs around 2100 h daily, may constitute a signal initiating normal sleep onset.

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Selected References

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  1. Anton-Tay F., Chou C., Anton S., Wurtman R. J. Brain serotonin concentration: elevation following intraperitoneal administration of melatonin. Science. 1968 Oct 11;162(3850):277–278. doi: 10.1126/science.162.3850.277. [DOI] [PubMed] [Google Scholar]
  2. Arendt J., Broadway J. Light and melatonin as zeitgebers in man. Chronobiol Int. 1987;4(2):273–282. doi: 10.3109/07420528709078534. [DOI] [PubMed] [Google Scholar]
  3. Brzezinski A., Seibel M. M., Lynch H. J., Deng M. H., Wurtman R. J. Melatonin in human preovulatory follicular fluid. J Clin Endocrinol Metab. 1987 Apr;64(4):865–867. doi: 10.1210/jcem-64-4-865. [DOI] [PubMed] [Google Scholar]
  4. Cagnacci A., Elliott J. A., Yen S. S. Melatonin: a major regulator of the circadian rhythm of core temperature in humans. J Clin Endocrinol Metab. 1992 Aug;75(2):447–452. doi: 10.1210/jcem.75.2.1639946. [DOI] [PubMed] [Google Scholar]
  5. Claustrat B., Brun J., David M., Sassolas G., Chazot G. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatry. 1992 Oct 15;32(8):705–711. doi: 10.1016/0006-3223(92)90300-o. [DOI] [PubMed] [Google Scholar]
  6. Czeisler C. A., Dumont M., Duffy J. F., Steinberg J. D., Richardson G. S., Brown E. N., Sánchez R., Ríos C. D., Ronda J. M. Association of sleep-wake habits in older people with changes in output of circadian pacemaker. Lancet. 1992 Oct 17;340(8825):933–936. doi: 10.1016/0140-6736(92)92817-y. [DOI] [PubMed] [Google Scholar]
  7. Dollins A. B., Lynch H. J., Wurtman R. J., Deng M. H., Kischka K. U., Gleason R. E., Lieberman H. R. Effect of pharmacological daytime doses of melatonin on human mood and performance. Psychopharmacology (Berl) 1993;112(4):490–496. doi: 10.1007/BF02244899. [DOI] [PubMed] [Google Scholar]
  8. Greenblatt D. J., Harmatz J. S., Engelhardt N., Shader R. I. Pharmacokinetic determinants of dynamic differences among three benzodiazepine hypnotics. Flurazepam, temazepam, and triazolam. Arch Gen Psychiatry. 1989 Apr;46(4):326–332. doi: 10.1001/archpsyc.1989.01810040032006. [DOI] [PubMed] [Google Scholar]
  9. Hoddes E., Zarcone V., Smythe H., Phillips R., Dement W. C. Quantification of sleepiness: a new approach. Psychophysiology. 1973 Jul;10(4):431–436. doi: 10.1111/j.1469-8986.1973.tb00801.x. [DOI] [PubMed] [Google Scholar]
  10. James S. P., Mendelson W. B., Sack D. A., Rosenthal N. E., Wehr T. A. The effect of melatonin on normal sleep. Neuropsychopharmacology. 1987 Dec;1(1):41–44. doi: 10.1016/0893-133x(87)90008-x. [DOI] [PubMed] [Google Scholar]
  11. James S. P., Sack D. A., Rosenthal N. E., Mendelson W. B. Melatonin administration in insomnia. Neuropsychopharmacology. 1990 Feb;3(1):19–23. [PubMed] [Google Scholar]
  12. Koelega H. S. Benzodiazepines and vigilance performance: a review. Psychopharmacology (Berl) 1989;98(2):145–156. doi: 10.1007/BF00444684. [DOI] [PubMed] [Google Scholar]
  13. Lewy A. J., Ahmed S., Jackson J. M., Sack R. L. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int. 1992 Oct;9(5):380–392. doi: 10.3109/07420529209064550. [DOI] [PubMed] [Google Scholar]
  14. Lieberman H. R., Waldhauser F., Garfield G., Lynch H. J., Wurtman R. J. Effects of melatonin on human mood and performance. Brain Res. 1984 Dec 10;323(2):201–207. doi: 10.1016/0006-8993(84)90290-7. [DOI] [PubMed] [Google Scholar]
  15. Nickelsen T., Demisch L., Demisch K., Radermacher B., Schöffling K. Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial. J Pineal Res. 1989;6(4):325–334. doi: 10.1111/j.1600-079x.1989.tb00428.x. [DOI] [PubMed] [Google Scholar]
  16. Petrie K., Conaglen J. V., Thompson L., Chamberlain K. Effect of melatonin on jet lag after long haul flights. BMJ. 1989 Mar 18;298(6675):705–707. doi: 10.1136/bmj.298.6675.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Viswanathan M., Laitinen J. T., Saavedra J. M. Expression of melatonin receptors in arteries involved in thermoregulation. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6200–6203. doi: 10.1073/pnas.87.16.6200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Waldhauser F., Lieberman H. R., Lynch H. J., Waldhauser M., Herkner K., Frisch H., Vierhapper H., Waldhäusl W., Schemper M., Wurtman R. J. A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or cortisol. Neuroendocrinology. 1987 Aug;46(2):125–130. doi: 10.1159/000124808. [DOI] [PubMed] [Google Scholar]
  19. Waldhauser F., Weiszenbacher G., Frisch H., Zeitlhuber U., Waldhauser M., Wurtman R. J. Fall in nocturnal serum melatonin during prepuberty and pubescence. Lancet. 1984 Feb 18;1(8373):362–365. doi: 10.1016/s0140-6736(84)90412-4. [DOI] [PubMed] [Google Scholar]
  20. Walsh J. K., Schweitzer P. K., Parwatikar S. Effects of lorazepam and its withdrawal on sleep, performance, and subjective state. Clin Pharmacol Ther. 1983 Oct;34(4):496–500. doi: 10.1038/clpt.1983.203. [DOI] [PubMed] [Google Scholar]
  21. Wilkinson R. Some factors influencing the effect of environmental stressors upon performance. Psychol Bull. 1969 Oct;72(4):260–272. doi: 10.1037/h0028029. [DOI] [PubMed] [Google Scholar]

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